This invention relates to calcification-resistant bioprosthetic implants and to a process for preparing them. More particularly, the invention concerns calcification-resistant bioprosthetic heart valves prepared from naturally derived biological materials.
Bioprosthetic heart valves, such as glutaraldehyde preserved porcine heart valves, have overcome numerous problems associated with mechanical and homograft heart valves. These bioprosthetic valves are quite stable and non-antigenic, have a remarkable durability and have physical characteristics which closely mimic the natural valves.
An alternative technique for the tanning or preservation of animal hides and tissues involves the use of metallic salts. Chrome tanning, for example, has been employed for many years in the leather industry. (See, e.g., U.S. Pat. No. 1,892,410.) Ferric, chromium and aluminum salts have been used for tanning naturally derived collagen, which may be used for preparing implantable prosthetic articles. (See U.S. Pat. No. 4,097,234.) Dardik, et al., in U.S. Pat. No. 3,974,526, describe the preparation of bioprosthetic vascular grafts from veins and arteries obtained from the umbilical cord. Among the reagents disclosed for hardening or tanning the vessels is chromium oxide.
A recurrent problem with such bioprosthetic heart valves has been their tendency toward calcification in vivo. This problem has been particularly prevalent in children, leading some to recommend against the use of bioprosthetic heart valves in children.
Various procedures for mitigating calcification of bioprosthetic heart valves have been proposed. For example, Lentz et al., in U.S. Pat. No. 4,323,358, disclose the treatment of implantable glutaraldehyde-fixed natural tissues (including porcine heart valves) with a soluble salt of a sulfated higher aliphatic alcohol to inhibit calcification after implantation. Nimni et al., in U.S. Pat. No. 4,378,224, disclose a procedure for inhibiting calcification of bioprosthetic tissues which involves cross-linking the tissue with a sulfated protein-polysaccharide, such as chondroitin sulfate. In U.S. Pat. No. 4,481,009, A. S. Nashef discloses a calcification mitigation procedure which comprises incorporating a biocompatible polymer into a bioprosthetic tissue prior to implantation tissue. Dewanjee et al., in U.S. Pat. No. 4,553,974, describe a multi-step procedure for treating biological tissues to inhibit calcification. This procedure involves treating the tissue with a surfactant, washing to remove the surfactant, fixing the tissue with glutaraldehyde, treating with a calcification inhibitor, such as an amino diphosphonate and treating the tissue with a reducing agent. U.S. Pat. No. 4,648,881, Carpentier et al., teaches that calcification of implanted biological tissue can be mitigated by avoiding contact of the tissues with phosphate-containing solutions, at least during the latter stages of their preparation. This patent also teaches that treatment of the tissue with a calcium-competitive divalent cation inhibits calcification of the implanted tissue.
A need continues to exist for a convenient, reliable and effective process for preparing calcification-resistant bioprosthetic implants, such as heart valves. Such a procedure should not deleteriously affect the durability, biocompatibility or physical characteristics of the bioprosthesis, and should be amendable to use in a commercial production process.